Using Electronic Health Record Data to Determine the Safety of Aqueous Humor Liquid Biopsies for Molecular Analyses.

Purpose: Knowing the surgical safety of anterior chamber liquid biopsies will support the increased use of proteomics and other molecular analyses to better understand disease mechanisms and therapeutic responses in patients and clinical trials. Manual review of operative notes from different surgeons and procedures in electronic health records (EHRs) is cumbersome, but free-text software tools could facilitate efficient searches. Design: Retrospective case series. Participants: A total of 1418 aqueous humor liquid biopsies from patients undergoing intraocular surgery. Methods: Free-text EHR searches were performed using the Stanford Research Repository cohort discovery tool to identify complications associated with anterior chamber paracentesis and subsequent endophthalmitis. Complications of the surgery unrelated to the biopsy were not reviewed. Main Outcome Measures: Biopsy-associated intraoperative complications and endophthalmitis. Results: A total of 1418 aqueous humor liquid biopsies were performed by 17 experienced surgeons. EHR free-text searches were 100% error-free for surgical complications, >99% for endophthalmitis (<1% false positive), and >93.6% for anesthesia type, requiring manual review for only a limited number of cases. More than 85% of cases were performed under local anesthesia without ocular muscle akinesia. Although the most common indication was cataract (50.1%), other diagnoses included glaucoma, diabetic retinopathy, uveitis, age-related macular degeneration, endophthalmitis, retinitis pigmentosa, and uveal melanoma. A 50- to 100-µL sample was collected in all cases using either a 30-gauge needle or a blunt cannula via a paracentesis. The median follow-up was >7 months. There was only one minor complication (0.07%) identified: a case of a small tear in Descemet membrane without long-term sequelae. No other complications occurred, including other corneal injuries, lens or iris trauma, hyphema, or suprachoroidal hemorrhage. There was no case of postoperative endophthalmitis. Conclusions: Anterior chamber liquid biopsy during intraocular surgery is a safe procedure and may be considered for large-scale collection of aqueous humor samples for molecular analyses. Free-text EHR searches are an efficient approach to reviewing intraoperative procedures. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Clinical outcomes following transtibial medial meniscal root repair are maintained at long-term follow-up.

PURPOSE: To evaluate long-term outcomes of patients treated with posterior medial meniscal root tear (PMMRT) repair through assessment of functional outcome scores and to identify patient surgical and magnetic resonance imaging (MRI) characteristics associated with improved outcomes. METHODS: This was a single-centre, retrospective study evaluating patients who had undergone a PMMR repair using a transtibial suture pullout technique with two locking cinch sutures. This was performed as a follow-up to previously published 2-year and 5-year outcome studies, using the same cohort. All patients from the prior short-term and midterm studies were invited to participate. Patient-reported outcome (PROs) scores, including the International Knee Documentation Committee (IKDC) and Lysholm scores, were collected. Previously collected demographic data were updated based on review of the electronic medical record. Patient outcomes were assessed preoperatively, as well as at 2-year, 5-year and 8-year postoperatively. MRI outcome measurements were assessed at 2-year and 5-year follow-ups. All statistical analysis was performed using SPSS version 26. RESULTS: Seventeen patients of the original 18 patients (94.4%) were included in the final analysis. Additionally, three patients who had additional ipsilateral surgery were excluded from the analysis of PROs. The IKDC score significantly increased from 44.7 ± 11.6 at preoperative baseline to 71.2 ± 21.3 at 8-year post-operation (p = 0.001). There were no significant differences in IKDC score between 2-year and 8-year follow-ups (p = n.s.) or 5-year and 8-year follow-ups (p = n.s.). The Lysholm score significantly increased from 49.6 ± 7.3 at preoperative baseline to 76.4 ± 17.2 at 8-year follow-up (p < 0.001). There was no significant difference in Lysholm scores between 2-year and 8-year follow-ups (p = n.s.) or 5-year and 8-year follow-ups (p = n.s.). A linear regression analysis found that 5-year IKDC scores were significantly correlated with 8-year IKDC scores (ß = 0.681, p = 0.038). At 8-year follow-up, four (23.5%) patients required additional procedures on their operative knee (one total knee arthroplasty conversion). CONCLUSION: Patients treated with repair of PMMRT had maintenance of clinical outcome improvements at long-term follow-up despite worsening MRI outcomes at short-term and medium-term follow-ups. While a high proportion of patients required additional procedures on their operative knee at 8-year follow-up, few of these patient's additional procedures were related to failure of their primary surgery. Providers and patients may expect durable clinical outcomes following the repair of PMMRT, irrespective of radiographic appearance. LEVEL OF EVIDENCE: Level IV.

Matrix-Induced Autologous Chondrocyte Implantation Versus Autologous Chondrocyte Implantation of the Knee A Retrospective Comparison.

OBJECTIVE: The purpose of this study was to compare the short-term clinical outcomes of matrix-induced autologous chondrocyte implantation (MACI) to those seen following traditional autologous chondrocyte implantation (ACI) in the management of symptomatic cartilage lesions of the knee. METHODS: This was a retrospective cohort study of patients who underwent either ACI or MACI from January 2011 to March 2018. Patients with a minimum postoperative follow-up of 18 months were contacted. Demographic information, intraoperative findings, and patient-reported functional outcomes scores were collected. Comparisons were made between the two cell-based cartilage repair techniques. RESULTS: Fifty-six patients were included in the study (39 ACI, 17 MACI). Visual analog scale (VAS) for pain scores improved significantly in both groups, with MACI patients demonstrating significantly lower postoperative pain scores compared to those treated with ACI. In the ACI group, there was a decrease in the Tegner Activity score compared to the preoperative baseline, while no significant difference was seen between pre- and postoperative activity levels in the MACI group. Patients were generally satisfied with the outcome of their procedures, and there was no significant difference in satisfaction between groups. No patients re-quired additional surgery during the follow-up period. CONCLUSION: Both ACI and MACI demonstrated good short-term postoperative clinical results with improved pain and activity levels compared to the preoperative baseline. Patients treated with the MACI technique demonstrated greater reductions in pain scores compared to ACI, and while ACI resulted in a decrease in levels of postoperative activity, activity levels for MACI remained stable.

Total hip arthroplasty outcomes in Ehlers-Danlos patients: data from the Statewide Planning and Research Cooperative System.

INTRODUCTION: Ehlers-Danlos syndromes (EDS) are genetic connective tissue disorders affecting multiple organ systems that frequently result in connective tissue hyperlaxity and early osteoarthritis. Short- and long-term outcomes after primary total hip arthroplasty (THA) in this patient population remain poorly characterised. The primary purpose of this study is to compare postoperative outcomes and survivorship after primary THA in patients with and without EDS. METHODS: The New York Statewide Planning and Research Cooperative System (SPARCS) database was queried for all patients undergoing primary elective THA between September 2009 and December 2020. Patients with EDS were identified using ICD9 and ICD10 diagnosis codes. Given the relatively low incidence of EDS in this patient population, the cohort was propensity-matched 1:10 to patients without diagnosis of EDS based on demographics characteristics and medical comorbidities as measured by the Elixhauser Comorbidity Index. RESULTS: A total of 66 THA patients with and 660 without EDS were included in each group after 1:10 propensity-matching. There were no significant differences in baseline characteristics or THA indications. Early postoperative outcomes such as length of hospital stay and discharge disposition were similar. Emergency Room visits and inpatient readmission rates at 3 months postoperatively did not significantly differ between groups. Patients with EDS had a higher overall revision rate compared to those without (15.0% vs. 3.2%, p < 0.001). Revision free survival after primary THA in patients with EDS was significantly lower than those without EDS at 9-year follow-up. Cox proportional hazard regression demonstrated EDS patients had 7-times higher risk of revision (hazard ratio [HR] 7.43; 95% CI, 3.46-16.00; p < 0.001). Lastly, revision due to instability insignificantly trended higher in the EDS cohort (HR 2.29; 95% CI, 0.95-5.49; p = 0.063). CONCLUSIONS: EDS patients undergoing primary THA have increased rate of all cause revision and demonstrate decreased revision free survival compared to non-EDS THA patients.

Do Patients With Insulin-Dependent and Non-Insulin-Dependent Diabetes Have Different Risks for Complications After Total Ankle Arthroplasty?

BACKGROUND: Patients with diabetes undergoing total ankle arthroplasty tend to be at greater risk for complications than those without diabetes. However, the effect of diabetes severity and how it impacts the risk for perioperative complications is less clear. The purpose of this study was to compare (1) complications, (2) length of hospital stay, and (3) readmissions within 30 days for total ankle arthroplasty (TAA) patients without diabetes, patients with non-insulin-dependent diabetes, and patients with insulin-dependent diabetes. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, a total of 1803 patients undergoing TAA between 2007 and 2019 were collected. The relationship between diabetes status (no diabetes [n = 1,589], insulin-dependent [n = 169], and non-insulin-dependent [n = 45]) and outcomes were compared. Multivariate linear regression models were used to adjust for confounding variables such as age, sex, race, body mass index, smoking, steroid use, hypertension, chronic obstructive pulmonary disease, anesthesia type, dyspnea, and outpatient status. Statistical significance was set at P <.05. RESULTS: Insulin-dependent diabetes was an independent risk factor for increased odds of infection within 30 days (odds ratio 6.47, 95% CI 0.79-33.66; P = .043). Hospital length of stay was also increased in patients with non-insulin-dependent diabetes (ß = 0.21, 95% CI 0.02-0.40; P = .031) and insulin-dependent diabetes (ß = 0.40, 95% CI 0.04-0.76; P = .028). However, neither diabetic state demonstrated a statistically significant increase in readmissions or wound complications within 30 days. CONCLUSION: Patients with insulin-dependent diabetes included in this cohort were at increased risk of having an infection within 30 days after TAA. Additionally, patients with diabetes status had an increased hospital length of stay. These results can inform patients on their potential outcomes after total ankle arthroplasty based on their diabetes status.

Polyvinyl alcohol hydrogel implant for the treatment of hallux rigidus is associated with a high complication rate and moderate failure rate at short-term follow-up: a systematic review.

PURPOSE: Moderate-to-severe hallux rigidus is a debilitating pathology that is optimally treated with surgical intervention. Arthrodesis produces reliable clinical outcomes but is limited by restriction in 1st metatarsophalangeal joint range of motion. The advent of polyvinyl alcohol hydrogel (PVA) implants have produced early promise based on initial trials, but more recent studies have called into question the efficacy of this procedure. The purpose of this systematic review was to evaluate the clinical and radiological outcomes following the use of PVA for hallux rigidus. METHODS: The MEDLINE, EMBASE and Cochrane library databases were systematically reviewed using the preferred reporting items for systematic reviews and meta-analyses guidelines. 18 studies were included. RESULTS: In total, 1349 patients (1367 feet) underwent PVA at a weighted mean follow-up of 24.1 ± 11.1 months. There were 168 patients (169 feet) included in the cheilectomy cohort and 322 patients (322 feet) included in the arthrodesis cohort. All 3 cohorts produced comparable improvements in subjective clinical outcomes. Postoperative imaging findings in the PVA cohort included joint space narrowing, peri-implant fluid, peri-implant edema and erosion of the proximal phalanx. The complication rate in the PVA cohort, cheilectomy cohort and arthrodesis cohort was 27.9%, 11.8% and 24.1%, respectively. The failure rates in the PVA cohort, cheilectomy cohort and arthrodesis cohort was 14.8%, 0.3% and 9.0%, respectively. CONCLUSION: This systematic review demonstrated that PVA produced a high complication rate (27.9%) together with concerning postoperative imaging findings at short-term follow-up. In addition, a moderate failure rate (14.8%) and secondary surgical procedure rate (9.5%) was noted for the PVA cohort. The findings of this review calls into question the efficacy and safety of PVA for the treatment of hallux rigidus. LEVEL OF EVIDENCE: IV.

Resilient anatomy and local plasticity of naive and stress haematopoiesis.

The bone marrow adjusts blood cell production to meet physiological demands in response to insults. The spatial organization of normal and stress responses are unknown owing to the lack of methods to visualize most steps of blood production. Here we develop strategies to image multipotent haematopoiesis, erythropoiesis and lymphopoiesis in mice. We combine these with imaging of myelopoiesis1 to define the anatomy of normal and stress haematopoiesis. In the steady state, across the skeleton, single stem cells and multipotent progenitors distribute through the marrow enriched near megakaryocytes. Lineage-committed progenitors are recruited to blood vessels, where they contribute to lineage-specific microanatomical structures composed of progenitors and immature cells, which function as the production sites for each major blood lineage. This overall anatomy is resilient to insults, as it was maintained after haemorrhage, systemic bacterial infection and granulocyte colony-stimulating factor (G-CSF) treatment, and during ageing. Production sites enable haematopoietic plasticity as they differentially and selectively modulate their numbers and output in response to insults. We found that stress responses are variable across the skeleton: the tibia and the sternum respond in opposite ways to G-CSF, and the skull does not increase erythropoiesis after haemorrhage. Our studies enable in situ analyses of haematopoiesis, define the anatomy of normal and stress responses, identify discrete microanatomical production sites that confer plasticity to haematopoiesis, and uncover unprecedented heterogeneity of stress responses across the skeleton.

Macrophages coordinate immune response to laser-induced injury via extracellular traps.

BACKGROUND: Retinal degeneration results from disruptions in retinal homeostasis due to injury, disease, or aging and triggers peripheral leukocyte infiltration. Effective immune responses rely on coordinated actions of resident microglia and recruited macrophages, critical for tissue remodeling and repair. However, these phagocytes also contribute to chronic inflammation in degenerated retinas, yet the precise coordination of immune response to retinal damage remains elusive. Recent investigations have demonstrated that phagocytic cells can produce extracellular traps (ETs), which are a source of self-antigens that alter the immune response, which can potentially lead to tissue injury. METHODS: Innovations in experimental systems facilitate real-time exploration of immune cell interactions and dynamic responses. We integrated in vivo imaging with ultrastructural analysis, transcriptomics, pharmacological treatments, and knockout mice to elucidate the role of phagocytes and their modulation of the local inflammatory response through extracellular traps (ETs). Deciphering these mechanisms is essential for developing novel and enhanced immunotherapeutic approaches that can redirect a specific maladaptive immune response towards favorable wound healing in the retina. RESULTS: Our findings underscore the pivotal role of innate immune cells, especially macrophages/monocytes, in regulating retinal repair and inflammation. The absence of neutrophil and macrophage infiltration aids parenchymal integrity restoration, while their depletion, particularly macrophages/monocytes, impedes vascular recovery. We demonstrate that macrophages/monocytes, when recruited in the retina, release chromatin and granular proteins, forming ETs. Furthermore, the pharmacological inhibition of ETosis support retinal and vascular repair, surpassing the effects of blocking innate immune cell recruitment. Simultaneously, the absence of ETosis reshapes the inflammatory response, causing neutrophils, helper, and cytotoxic T-cells to be restricted primarily in the superficial capillary plexus instead of reaching the damaged photoreceptor layer. CONCLUSIONS: Our data offer novel insights into innate immunity's role in responding to retinal damage and potentially help developing innovative immunotherapeutic approaches that can shift the immune response from maladaptive to beneficial for retinal regeneration.

A mitochondrial NADPH-cholesterol axis regulates extracellular vesicle biogenesis to support hematopoietic stem cell fate.

Mitochondrial fatty acid oxidation (FAO) is essential for hematopoietic stem cell (HSC) self-renewal; however, the mechanism by which mitochondrial metabolism controls HSC fate remains unknown. Here, we show that within the hematopoietic lineage, HSCs have the largest mitochondrial NADPH pools, which are required for proper HSC cell fate and homeostasis. Bioinformatic analysis of the HSC transcriptome, biochemical assays, and genetic inactivation of FAO all indicate that FAO-generated NADPH fuels cholesterol synthesis in HSCs. Interference with FAO disturbs the segregation of mitochondrial NADPH toward corresponding daughter cells upon single HSC division. Importantly, we have found that the FAO-NADPH-cholesterol axis drives extracellular vesicle (EV) biogenesis and release in HSCs, while inhibition of EV signaling impairs HSC self-renewal. These data reveal the existence of a mitochondrial NADPH-cholesterol axis for EV biogenesis that is required for hematopoietic homeostasis and highlight the non-stochastic nature of HSC fate determination.

The Role of Hyaluronan/Receptor for Hyaluronan-Mediated Motility Interactions in the Modulation of Macrophage Polarization and Cartilage Repair.

Hyaluronan (HA), a negatively charged linear glycosaminoglycan, is a key macromolecular component of the articular cartilage extracellular matrix. The differential effects of HA are determined by a spatially/temporally regulated display of HA receptors, such as CD44 and receptor for hyaluronan-mediated motility (RHAMM). HA signaling through CD44 with RHAMM has been shown to stimulate inflammation and fibrotic processes. This study shows an increased expression of RHAMM in proinflammatory macrophages. Interfering with HA/RHAMM interactions using a 15-mer RHAMM-mimetic, HA-binding peptide, together with high-molecular-weight (HMW) HA reduced the expression and release of inflammatory markers and increased the expression of anti-inflammatory markers in proinflammatory macrophages. HA/RHAMM interactions were interfered in vivo during the regeneration of a full-thickness cartilage defect after microfracture surgery in rabbits using three intra-articular injections of 15-mer RHAMM-mimetic. HA-binding peptide together with HMWHA reduced the number of proinflammatory macrophages and increased the number of anti-inflammatory macrophages in the injured knee joint and greatly improved the repair of the cartilage defect compared with intra-articular injections of HMWHA alone. These findings suggest that HA/RHAMM interactions play a key role in cartilage repair/regeneration via stimulating inflammatory and fibrotic events, including increasing the ratio of proinflammatory/anti-inflammatory macrophages. Interfering with these interactions reduced inflammation and greatly improved cartilage repair.

A narrative review of the Medtronic Hugo RAS and technical comparison with the Intuitive da Vinci robotic surgical system.

Medtronic launched the Hugo Robotic-Assisted Surgery (RAS) System in 2021, offering a modular alternative to the incumbent market leader in surgical robotics, the Intuitive da Vinci (dV) surgical system. A detailed technical review of the Hugo RAS was conducted to explore the strengths and weaknesses of this new robotic surgical system. Each component of the system-vision tower, arm cart, and surgeon console-was compared against the existing dV systems. The docking process, instrumentation, and external arm movement trajectories were analyzed. The modular Hugo RAS provides the possibility of operating using up to four arm carts. It has certain design features that are unique to itself, and others that have been implemented to address the shortcomings of the dV Si. While Medtronic's first-generation robot offers distinct advantages over the older Intuitive systems, the true test of its mettle will be its performance compared to the latest dV Xi.

Postoperative complications in rheumatic disease patients undergoing arthroscopy on immunosuppression.

BACKGROUND: There are currently no guidelines on peri-arthroscopic management of immunosuppressive (IS) treatment in rheumatic disease patients. PURPOSE: The purpose of this study is to characterize the rheumatic disease patient population undergoing arthroscopy, compare the incidence of postoperative complications among patients who either remained on IS perioperatively, held IS perioperatively or were not on IS at baseline, and compare the incidence of postoperative complications by rheumatic disease type, medication type, and procedure. METHODS: We conducted a retrospective review of all arthroscopic sports medicine surgeries in patients with a rheumatic disease diagnosis at our institution over an 11-year period. Patients on IS at baseline were grouped into those who remained on IS perioperatively or held all IS before the date of their surgery. These two groups were compared to patients who were not on IS at baseline. Incidence of postoperative complications was calculated for the three cohorts and by medication class, rheumatic disease type, and procedure risk. Analysis of variance (ANOVA), chi-squared, and Fisher's exact tests were used to determine the statistical significance of between-group differences in postoperative complication incidence. RESULTS: We identified 1,316 rheumatic disease patients undergoing arthroscopy, with 214 of them taking IS medications at baseline. In total, 8.4% (n = 110) remained on IS perioperatively, 7.9% (n = 104) held IS perioperatively, and 83.7% (n = 1102) were not on IS at baseline. In all cohorts, seven patients experienced postoperative complications; six of whom experienced infections. Two (1.82%) occurred in patients remaining on IS perioperatively, zero infections occured in patients who held all IS, and four (0.36%) occured in patients who were not on any IS at baseline. There was no statistically significant difference in postoperative infections or complication rates among the three cohorts or further subgroups. CONCLUSION: The risk of postoperative complications including infectious, major, and minor complications in patients on IS at the time of arthroscopy is low and acceptable.

Stereotactic ablative body radiotherapy for primary kidney cancer (TROG 15.03 FASTRACK II): a non-randomised phase 2 trial.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a novel non-invasive alternative for patients with primary renal cell cancer who do not undergo surgical resection. The FASTRACK II clinical trial investigated the efficacy of SABR for primary renal cell cancer in a phase 2 trial. METHODS: This international, non-randomised, phase 2 study was conducted in seven centres in Australia and one centre in the Netherlands. Eligible patients aged 18 years or older had biopsy-confirmed diagnosis of primary renal cell cancer, with only a single lesion; were medically inoperable, were at high risk of complications from surgery, or declined surgery; and had an Eastern Cooperative Oncology Group performance status of 0-2. A multidisciplinary decision that active treatment was warranted was required. Key exclusion criteria were a pre-treatment estimated glomerular filtration rate of less than 30 mL/min per 1·73 m2, previous systemic therapies for renal cell cancer, previous high-dose radiotherapy to an overlapping region, tumours larger than 10 cm, and direct contact of the renal cell cancer with the bowel. Patients received either a single fraction SABR of 26 Gy for tumours 4 cm or less in maximum diameter, or 42 Gy in three fractions for tumours more than 4 cm to 10 cm in maximum diameter. The primary endpoint was local control, defined as no progression of the primary renal cell cancer, as evaluated by the investigator per Response Evaluation Criteria in Solid Tumours (version 1.1). Assuming a 1-year local control of 90%, the null hypothesis of 80% or less was considered not to be worthy of proceeding to a future randomised controlled trial. All patients who commenced trial treatment were included in the primary outcome analysis. This trial is registered with ClinicalTrials.gov, NCT02613819, and has completed accrual. FINDINGS: Between July 28, 2016, and Feb 27, 2020, 70 patients were enrolled and initiated treatment. Median age was 77 years (IQR 70-82). Before enrolment, 49 (70%) of 70 patients had documented serial growth on initial surveillance imaging. 49 (70%) of 70 patients were male and 21 (30%) were female. Median tumour size was 4·6 cm (IQR 3·7-5·5). All patients enrolled had T1-T2a and N0-N1 disease. 23 patients received single-fraction SABR of 26 Gy and 47 received 42 Gy in three fractions. Median follow-up was 43 months (IQR 38-60). Local control at 12 months from treatment commencement was 100% (p<0·0001). Seven (10%) patients had grade 3 treatment-related adverse events, with no grade 4 adverse events observed. Grade 3 treatment-related adverse events were nausea and vomiting (three [4%] patients), abdominal, flank, or tumour pain (four [6%]), colonic obstruction (two [3%]), and diarrhoea (one [1%]). No treatment-related or cancer-related deaths occurred. INTERPRETATION: To our knowledge, this is the first multicentre prospective clinical trial of non-surgical definitive therapy in patients with primary renal cell cancer. In a cohort with predominantly T1b or larger disease, SABR was an effective treatment strategy with no observed local failures or cancer-related deaths. We observed an acceptable side-effect profile and renal function after SABR. These outcomes support the design of a future randomised trial of SABR versus surgery for primary renal cell cancer. FUNDING: Cancer Australia Priority-driven Collaborative Cancer Research Scheme.

Trends in the treatment of proximal humerus fractures from 2010 to 2020.

BACKGROUND: The incidence of proximal humerus fractures (PHF) is continuing to rise due to shifts towards a more aged population as well as advancements in surgical treatment options. The purpose of this study is to examine and compare trends in the treatment of PHFs (nonoperative vs. operative; different surgical treatments) across different age groups over the last decade (2010-2020). METHODS: The New York Statewide Planning and Research Cooperative System (SPARCS) database was queried using International Classification of Diseases and Current Procedural Terminology codes to identify all patients presenting with or undergoing surgery for PHF between 2010 and 2020. Treatment trends, demographics, and insurance information were analyzed during the study period. Comparisons were made between operative and nonoperative trends with respect to the number and type of surgeries performed among 3 age groups: ≤49 years, 50-64 years, and ≥65 years. The rate of postoperative complications and reoperations was evaluated and compared among different surgical treatments for patients with a minimum 1-year postoperative follow-up. RESULTS: A total of 92,308 patients with a mean age of 67.8 ± 16.8 years were included. Over the last decade, there was no significant increase in the percentage of PHFs treated with surgery. A total of 15,523 PHFs (16.82%) were treated operatively, and these patients, compared with the nonoperative cohort, were younger (64.9 years vs. 68.4 years, P < .001), more likely to be White (80.2% vs. 74.7%, P < .001), and more likely to have private insurance (41.4% vs. 32.0%, P < .001). For patients ≤49 years old, trends in operative treatment have remained stable with internal fixation (IF) as the most used surgical modality. For patients 50-64 years old, we observed a gradual decline in the use of hemiarthroplasty (HA), with a corresponding increase in the use of reverse total shoulder arthroplasty (rTSA), but IF continued to be the most used operative modality. In patients over 65 years, a steep decline in the use of IF and HA was noted during the first half of the decade along with a significant exponential increase in the use of rTSA, which surpassed the use of IF in 2019. Despite the increase in the use of rTSA, no differences in rate of surgical complications were noted between rTSA and IF (χ2 = 0.245, P = .621) or reoperations (χ2 = 0.112, P = .730). CONCLUSION: Nonsurgical treatment remains the mainstay treatment of PHFs. Although there is no increase in the prevalence of operative treatment in patients ≥50 years in the last decade, there is an exponential increase in the use of rTSA with a corresponding decrease in HA and IF, a trend more substantial in patients ≥65 years compared with patients between 50 and 64 years.

Borderline Hip Dysplasia Is Not Associated With Significant Differences in Hip Survivorship or Patient-Reported Outcomes Following Primary Hip Arthroscopy for Femoroacetabular Impingement Syndrome: A Propensity-Matched Cohort Study.

PURPOSE: To compare hip survivorship and patient-reported outcomes after primary hip arthroscopy for femoroacetabular impingement syndrome (FAIS) in patients with versus without comorbid borderline hip dysplasia (BHD) at 2-year follow-up. METHODS: A retrospective matched-cohort study was conducted involving patients who underwent primary hip arthroscopy for FAIS with a single surgeon from 2010 to 2019. BHD was defined as lateral center edge angle (LCEA) of 20 to 25°. Subjects with BHD were matched 1:2 to controls without BHD on age, sex, body mass index, and preoperative modified Harris Hip Score (mHHS). Alpha angle, LCEA, Tönnis angle, and acetabular retroversion signs were measured on preoperative and/or postoperative hip radiographs. Patient-reported outcomes were assessed using the mHHS and the Non-Arthritic Hip Score. Hip survivorship, outcome scores, and achievement of the minimum clinically important difference were compared between groups using the Mann-Whitney U test or Fisher exact test, as appropriate. P values <.05 were considered significant. RESULTS: Thirty-one BHD subjects (mean age 36.8 years, 71.0% female) and 62 controls (mean age 38.0 years, 71.0% female) were included. There were no significant intergroup differences in demographics or preoperative radiographic measurements besides LCEA and Tönnis angle (all P > .05). Intraoperatively, subjects with BHD were found to have significantly shorter labral tears (mean 2.6 vs 2.8 clock-face hours, P = .048), but there were no significant intergroup differences in acetabular or femoral cartilage status (all P > .05). Postoperatively, there were no significant intergroup differences in rates of revision arthroscopy (BHD 6.5% vs control 11.3%) or conversion to total hip arthroplasty (BHD 9.7% vs control 1.6%), in 2-year improvement of the mHHS and Non-Arthritic Hip Score, or in minimum clinically important difference achievement rates (all P > .05). CONCLUSIONS: BHD is not associated with a significant difference in hip survivorship or patient-reported outcomes following primary hip arthroscopy for FAIS. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Toric Monofocal Intraocular Lenses for the Correction of Astigmatism during Cataract Surgery: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature evaluating the visual and refractive outcomes and rotational stability of eyes implanted with toric monofocal intraocular lenses (IOLs) for the correction of keratometric astigmatism during cataract surgery and to compare those outcomes with outcomes of eyes implanted with nontoric monofocal IOLs and other astigmatism management methods performed during cataract surgery. This assessment was restricted to the toric IOLs available in the United States. METHODS: A literature search of English-language publications in the PubMed database was last conducted in July 2022. The search identified 906 potentially relevant citations, and after review of the abstracts, 63 were selected for full-text review. Twenty-one studies ultimately were determined to be relevant to the assessment criteria and were selected for inclusion. The panel methodologist assigned each a level of evidence rating; 12 studies were rated level I and 9 studies were rated level II. RESULTS: Eyes implanted with toric IOLs showed excellent postoperative uncorrected distance visual acuity (UCDVA), reduction of postoperative refractive astigmatism, and good rotational stability. Uncorrected distance visual acuity was better and postoperative cylinder was lower with toric IOLs, regardless of manufacturer, when compared with nontoric monofocal IOLs. Correcting pre-existing astigmatism with toric IOLs was more effective and predictable than using corneal relaxing incisions (CRIs), especially in the presence of higher magnitudes of astigmatism. CONCLUSIONS: Toric monofocal IOLs are effective in neutralizing pre-existing corneal astigmatism at the time of cataract surgery and result in better UCDVA and significant reductions in postoperative refractive astigmatism compared with nontoric monofocal IOLs. Toric IOLs result in better astigmatic correction than CRIs, particularly at high magnitudes of astigmatism. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Effect of Simultaneous Endothelial Keratoplasty and Cataract Surgery: A Secondary Analysis of the Descemet Endothelial Thickness Comparison Trial.

PURPOSE: Combining cataract surgery with endothelial keratoplasty (triple EK) is a common practice and may be safer because it commits the patient to only one surgery. This study aimed to determine whether outcomes of pseudophakic endothelial keratoplasty and triple EK have similar outcomes. METHODS: This was a non-prespecified secondary analysis of a multicenter, double-masked, randomized, controlled clinical trial. Enrollment centers included the Casey Eye Institute at Oregon Health and Sciences University and the Byers Eye Institute at Stanford University. Patients with damaged or diseased endothelium and were considered good candidates for either Descemet membrane endothelial keratoplasty or ultrathin Descemet stripping automated endothelial keratoplasty were randomized to one of the two surgeries 1-2 days prior to surgery. If the patient had a cataract, they underwent simultaneous cataract surgery. The primary outcome was visual acuity at 6 months. Visual acuity at 3, 12, and 24 months, 3, 6, 12, and 24 month endothelial cell density and intraoperative and postoperative complications were also recorded. RESULTS: Those who had pseudophakic EK generally were older, more likely to be male, and more likely to have worse baseline vision with higher corneal densitometry values. After controlling for baseline visual acuity and type of keratoplasty, those that underwent Triple-EK had 0.09 better LogMAR lines better visual acuity at 6 (95% CI -0.17 to -0.10; P = 0.02) and 12 months (95% CI -0.21 to -0.07; P = 0.03). Although those receiving Triple- EK had nearly one-half LogMAR line better visual acuity at 24 months, it was no longer statistically significant (95% CI -0.20 to -0.05; P = 0.36). There was no statistically significant difference in ECD between groups at any timepoint. Those undergoing triple EK were more likely to have at least one adverse event (P = 0.02). CONCLUSIONS: Earlier intervention with Triple-EK may improve visual acuity outcomes after endothelial keratoplasty compared with staged procedures, but may also increase the risks of adverse events including the need for re-bubble.

Discovery of KB-0742, a Potent, Selective, Orally Bioavailable Small Molecule Inhibitor of CDK9 for MYC-Dependent Cancers.

Transcriptional deregulation is a hallmark of many cancers and is exemplified by genomic amplifications of the MYC family of oncogenes, which occur in at least 20% of all solid tumors in adults. Targeting of transcriptional cofactors and the transcriptional cyclin-dependent kinase (CDK9) has emerged as a therapeutic strategy to interdict deregulated transcriptional activity including oncogenic MYC. Here, we report the structural optimization of a small molecule microarray hit, prioritizing maintenance of CDK9 selectivity while improving on-target potency and overall physicochemical and pharmacokinetic (PK) properties. This led to the discovery of the potent, selective, orally bioavailable CDK9 inhibitor 28 (KB-0742). Compound 28 exhibits in vivo antitumor activity in mouse xenograft models and a projected human PK profile anticipated to enable efficacious oral dosing. Notably, 28 is currently being investigated in a phase 1/2 dose escalation and expansion clinical trial in patients with relapsed or refractory solid tumors.

SuRxgWell: study protocol for a randomized controlled trial of telemedicine-based digital cognitive behavioral intervention for high anxiety and depression among patients undergoing elective hip and knee arthroplasty surgery.

BACKGROUND: Mood disorders (anxiety, depression), sleep disorders, and catastrophizing lead to increased post-operative pain perception, increase in postoperative opioid consumption, decreased engagement with physical activity, and increased resource utilization in surgical patients. Psychosocial disorders significantly affect postoperative outcome. Unfortunately, studies focused on perioperative psychological assessment and treatment are scarce. We propose to test whether digital cognitive behavioral intervention (dCBI) can help surgical patients. dCBI such as RxWell™ is a proven treatment for mood disorders in medical patients such as reducing depression in patients with inflammatory bowel disease. We hypothesize that RxWell™ will also be effective in surgical patients. This study aims to test whether RxWell™ can improve preoperative mood disorders and subsequently reduce postoperative pain and opioid requirement in patients scheduled for primary total hip and knee arthroplasty (THA, TKA). We named the trial as the SuRxgWell trial. METHODS: This is a randomized, controlled trial that will enroll primary and unilateral THA or TKA patients with anxiety and/or depression symptoms before surgery to receive the SuRxgWell dCBI program and investigate its impact on postoperative outcomes including postoperative pain, anxiety, depression, sleep disorder, and catastrophizing. After signing an informed consent, subjects will be screened using the PROMIS questionnaires, and subjects with a T-score of ≥ 60 on the short Patient-Reported Outcomes Measurement Information System (PROMIS) 4a Anxiety and/or short PROMIS 4a Depression questionnaires will be randomized to either usual care (control group) or the cognitive behavioral intervention, RxWell™, plus usual care (intervention group). The control group will receive information on how to locate tools to address anxiety and depression, whereas the intervention group will have access to SuRxgWell 1 month prior to surgery and up to 3 months after surgery. The allocation will be 3:1 (intervention to control). Investigators will be blinded, but research coordinators approaching patients and research subjects will not. The primary outcome will be day of surgery anxiety or depression symptoms measured with the PROMIS Short Form v1.0 -Anxiety 4a/Depression and Generalized Anxiety Disorder Measure (GAD-7) and Patient Health Questionnaire (PHQ-8). Secondary end points include measuring other health-related quality of life outcomes including sleep disturbance, fatigue, ability to participate in social roles, pain interference, cognitive function, pain catastrophizing, and physical function. Other secondary outcomes include collecting data about preoperative and postoperative pain scores, and pain medication usage, and orthopedic functional recovery at baseline, day of surgery, and 1, 2, and 3 months after the surgery with the Pain Catastrophizing Scale, the Knee injury and Osteoarthritis Outcome Score (KOOS), and Hip injury and Osteoarthritis Outcome Score (HOOS). In addition, subjects will be asked to complete a GAD-7 and PHQ-8 questionnaires bi-weekly (via the RxWell™ app for the interventional group or REDCAP for the control group). Data about postsurgical complications, and resource utilization will also be recorded. We will also receive monthly reports measuring the usage and engagement of RxWell use for each participant randomized to that arm. The primary hypotheses will be assessed with intention-to-treat estimates, and differences in primary outcome will be tested using independent two sample t-tests. This trial is registered to the ClinicalTrials.gov database (NCT05658796) and supported by the DAPM, UPMC Health Plan, and the NIH. DISCUSSION: Our trial will evaluate the feasibility of digital cognitive behavioral intervention as a perioperative tool to improve anxiety and depression before and after major orthopedic surgery in comparison to education. If digital cognitive behavioral intervention proves to be effective, this might have important clinical implications, reducing the incidence of chronic postsurgical pain and improving outcomes.

Osteolysis Following the Use of Polyetheretherketone Suture Anchors in Hand and Wrist Surgery: A Preliminary Study.

PURPOSE: The objective of this study was to investigate and describe the presence of osteolysis after implantation of polyetheretherketone (PEEK) suture anchors in the hand and wrist. METHODS: Patients who underwent hand or wrist surgery using PEEK suture anchor(s) at a large academic institution from January 2019 to January 2021 were identified. Patients without accessible intraoperative fluoroscopic imaging were excluded. Patient demographics, type of procedure, and suture anchor material were recorded. The suture anchor tunnel size was measured on sequential radiographs and recorded as percentage change. Descriptive statistics were used to summarize findings. RESULTS: A total of 26 PEEK suture anchors in 14 patients were included, with an average follow-up of 12.0 months (range, 1.5-24.1 months). Twenty-seven percent of the anchors (7/26) demonstrated osteolysis at final follow-up, as defined by enlargement of tunnel size by >30%. In all anchors, the tunnel size increased by 19.1% on average (range, -7.7% to 56.1%) by final follow-up. CONCLUSIONS: Polyetheretherketone suture anchors may be associated with the development of osteolysis in hand and wrist surgery. The clinical implications of osteolysis in the smaller bones of the hand and wrist remain unclear. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.